ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.4318C>T (p.Gln1440Ter)

dbSNP: rs45517337
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV000201035 SCV000255900 pathogenic Tuberous sclerosis 2 2014-08-28 criteria provided, single submitter clinical testing
GeneDx RCV000521569 SCV000617352 pathogenic not provided 2017-10-19 criteria provided, single submitter clinical testing The Q1440X nonsense variant in the TSC2 gene has been reported previously in association withtuberous sclerosis complex (TSC) (Au et al., 2007; TSC2 LOVD). This pathogenic variant is predictedto cause loss of normal protein function either through protein truncation or nonsense-mediatedmRNA decay. The Q1440X variant is not observed in large population cohorts (Lek et al., 2016). Therefore, the presence of Q1440X is consistent with the diagnosis of TSC in this individual.
Genome-Nilou Lab RCV000201035 SCV002040993 pathogenic Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000201035 SCV004296671 pathogenic Tuberous sclerosis 2 2024-04-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln1440*) in the TSC2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TSC2 are known to be pathogenic (PMID: 10205261, 17304050). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with tuberous sclerosis complex (PMID: 32313033). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 49524). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic.
Tuberous sclerosis database (TSC2) RCV000042784 SCV000066580 not provided Tuberous sclerosis syndrome no assertion provided curation

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